Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank.

BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

Background: The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. Methods: We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. Results: After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Conclusion: Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

The experiences and perspectives of people with gout on urate self-monitoring.

INTRODUCTION: Gout management remains suboptimal despite safe and effective urate-lowering therapy. Self-monitoring of urate may improve gout management, however, the acceptability of urate self-monitoring by people with gout is unknown. The aim of this study was to explore the experiences of urate self-monitoring in people with gout. METHODS: Semistructured interviews were conducted with people taking urate-lowering therapy (N = 30) in a 12-month trial of urate self-monitoring in rural and urban Australia. Interviews covered the experience of monitoring and its effect on gout self-management. Deidentified transcripts were analysed thematically. RESULTS: Participants valued the ability to self-monitor and gain more understanding of urate control compared with the annual monitoring ordered by their doctors. Participants indicated that self-monitoring at home was easy, convenient and informed gout self-management behaviours such as dietary modifications, hydration, exercise and medication routines. Many participants self-monitored to understand urate concentration changes in response to feeling a gout flare was imminent or whether their behaviours, for example, alcohol intake, increased the risk of a gout flare. Urate concentrations were shared with doctors mainly when they were above target to seek management support, and this led to allopurinol dose increases in some cases. CONCLUSION: Urate self-monitoring was viewed by people with gout as convenient and useful for independent management of gout. They believed self-monitoring achieved better gout control with a less restricted lifestyle. Urate data was shared with doctors at the patient's discretion and helped inform clinical decisions, such as allopurinol dose changes. Further research on implementing urate self-monitoring in routine care would enable an evaluation of its impact on medication adherence and clinical outcomes, as well as inform gout management guidelines. PATIENT OR PUBLIC CONTRIBUTION: One person with gout, who was not a participant, was involved in the study design by providing feedback and pilot testing the semistructured interview guide. In response to their feedback, subsequent modifications to the interview guide were made to improve the understandability of the questions from a patient perspective. No additional questions were suggested.

Association between low-density lipoprotein cholesterol levels and serum uric acid to serum creatinine ratio in Chinese male gout patients.

This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18-83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24-28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (ß = 0.67, 95% CI 0.35-0.98, P < 0.001). Moreover, LDL-C showed a significant positive correlation with SUA/SCr with a BMI of 28 or greater (ß = 0.30, 95% CI 0.05-0.55, P = 0.019). However, no association was found between LDL-C and SUA/SCr with a BMI of less than 24 (ß = 0.42, 95% CI - 0.03-0.86, P = 0.070). LDL-C levels were associated with SUA/SCr in Chinese male gout patients, but this correlation appeared inconsistent among different BMIs. Our findings suggest that LDL-C levels may be more noteworthy in overweight and/or obese male gout patients.

Nonlinear relationship between oxidative balance score and hyperuricemia: analyses of NHANES 2007-2018.

BACKGROUND: Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia. METHODS: We conducted a cross-sectional study involving 13,636 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings. RESULTS: Higher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship. CONCLUSION: This study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.

Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of metabolic syndrome among females: Results from NHANES 2007-2010 and 2017-2018.

OBJECTIVE: Known for anti-inflammatory and antioxidant properties, flavonoid has phytoestrogenic effects, but it is unclear whether its role in hyperuricemia and metabolic syndrome (MetS) differs by gender. Moreover, given the strong association between hyperuricemia and MetS, we aimed to explore whether flavonoid is a protective factor for hyperuricemia, independently of MetS, in different genders. METHODS: Data for 2007-2010 and 2017-2018 were obtained from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS). To assess the association among flavonoid, hyperuricemia, and MetS, multivariate logistic regression and subgroup analyses were conducted. Besides, to investigate whether the association between flavonoid and hyperuricemia was independent of MetS, multivariate logistic regression models were further conducted to explore the association between flavonoid and MetS among females with hyperuricemia and to investigate the association between flavonoid and hyperuricemia among females after excluding MetS. RESULT: Among 5356 females, anthocyanin intake was inversely associated with the prevalence of hyperuricemia (Q4 vs. Q1: OR 0.49, 95% CI 0.31 to 0.76), and MetS (Q4 vs. Q1: OR 0.68, 95% CI 0.50 to 0.93). Furthermore, subgroup analyses showed the beneficial association between anthocyanin and hyperuricemia among females aged 40 to 59 years and menopausal. However, among 5104 males, no significant association was observed after adjustment for covariates (Q4 vs. Q1: OR 0.81, 95% CI 0.56 to 1.18). While in 372 females with hyperuricemia, no significant association was found between MetS and anthocyanin (Q4 vs. Q1: OR 0.88, 95% CI 0.31 to 2.49). Meanwhile, among 3335 females after excluding MetS, there was still a significant association between anthocyanin and a lower prevalence of hyperuricemia (Q4 vs. Q1: OR 0.38, 95% CI 0.17 to 0.85). CONCLUSION: Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of MetS among females. Foods rich in anthocyanin should be emphasized for females, especially those aged 40 to 59 years and menopausal, which may be of potential significance in the prevention of hyperuricemia.

The Simultaneous Detection of Dopamine and Uric Acid In Vivo Based on a 3D Reduced Graphene Oxide-MXene Composite Electrode.

Dopamine (DA) and uric acid (UA) are essential for many physiological processes in the human body. Abnormal levels of DA and UA can lead to multiple diseases, such as Parkinson's disease and gout. In this work, a three-dimensional reduced graphene oxide-MXene (3D rGO-Ti3C2) composite electrode was prepared using a simple one-step hydrothermal reduction process, which could separate the oxidation potentials of DA and UA, enabling the simultaneous detection of DA and UA. The 3D rGO-Ti3C2 electrode exhibited excellent electrocatalytic activity towards both DA and UA. In 0.01 M PBS solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.74 µA·µM-1·cm-2 and a detection limit of 0.056 µM (S/N = 3), while the linear range of UA was 0.5-60 µM and 80-450 µM, with sensitivity of 2.96 and 0.81 µA·µM-1·cm-2, respectively, and a detection limit of 0.086 µM (S/N = 3). In 10% fetal bovine serum (FBS) solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.41 µA·µM-1·cm-2 and a detection limit of 0.091 µM (S/N = 3). The linear range of UA was 2-500 µM with a sensitivity of 0.11 µA·µM-1·cm-2 and a detection limit of 0.6 µM (S/N = 3). The modified electrode exhibited advantages such as high sensitivity, a strong anti-interference capability, and good repeatability. Furthermore, the modified electrode was successfully used for DA measurement in vivo. This could present a simple reliable route for neurotransmitter detection in neuroscience.

Serum urate change among gout patients treated with sodium-glucose cotransporter type 2 inhibitors vs. sulfonylurea: A comparative effectiveness analysis.

OBJECTIVE: To investigate the serum urate (SU) change among gout patients initiating SGLT2i, and to compare with sulfonylurea, the second-most widely used glucose-lowering medication after metformin. METHODS: We conducted a cohort study of patients with gout and baseline SU >6 mg/dL who had SU measured within 90 days before and after SGLT2i or sulfonylurea initiation. Using multivariable linear regression, we compared SU change among SGLT2i initiators between those with and without diabetes and then compared SU change between SGLT2i and sulfonylurea. RESULTS: We identified 28 patients with gout initiating SGLT2i (including 16 with diabetes) and 28 patients initiating sulfonylurea (all with diabetes). Among SGLT2i initiators, the mean within-group SU change was -1.8 (95 % CI, -2.4 to -1.1) mg/dL, including -1.2 (-1.8 to -0.6) mg/dL and -2.5 (-3.6 to -1.3) mg/dL among patients with and without diabetes, respectively, with an adjusted difference between those with and without diabetes of -1.4 (-2.4 to -0.5) mg/dL. The SU did not change after initiating sulfonylurea (+0.3 [-0.3 to 1.0] mg/dL). The adjusted SU change difference between SGLT2i vs. sulfonylurea initiation was -1.8 (-2.7 to -0.9) mg/dL in all patients. The SU reduction persisted regardless of urate-lowering therapy or diuretic use and the presence of diabetes, chronic kidney disease, or heart failure. CONCLUSION: Among patients with gout, SGLT2i was associated with a notable reduction in SU compared with sulfonylurea, with a larger reduction among patients without diabetes. With their proven cardiovascular-kidney-metabolic benefits, adding SGLT2i to current gout management could provide streamlined benefits for gout and its comorbidities.

Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk.

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Hypouricemia with hypercalciuria: Longitudinal study and review of the topic.

BACKGROUND AND OBJECTIVE: The association of hypouricemia and hypercalciuria is rare. In 1974 a new syndrome named Hypouricemia with hypercalciuria and decreased bone density was described. Afterwards, some cases with such association were published in which the fractional excretion of urate was higher than 20ml/100ml FGR. We have analyzed a series of children who were diagnosed with hypouricemia and hypercalciuria and who were monitored. The aim of this study was to determine whether our patients could be affected by the aforementioned syndrome or be carriers of a variant of idiopathic hypercalciuria. PATIENTS AND METHODS: Retrospective longitudinal study in which the medical records of eight patients (5V, 3M) diagnosed with hypouricemia and hypercalciuria in childhood. Clinical features at diagnosis, ultrasound and densitometric findings and selected biochemical variables were noted, with special emphasis on renal tubular handling of urate. Results were compared with 36 children with idiopathic hypercalciuria without hypouricemia (14V, 22M). RESULTS: In the hypouricemia group baseline urate levels were 1.9 (0.3) mg/dl (range: 1.5-2) and first day urine calcium/creatinine ratio 0.27 (0.05) mg/mg (range: 0.23-0.31). In all cases fractional urate excretion was less than 20ml/100ml FGR. The z-DMO values were less than -1 in 4/8 cases. At the last follow-up only three cases still had an elevated calcium/creatinine ratio and in all of them the urates levels was greater than 2mg/dl. The z-DMO value had improved in five cases and worsened in three others. In relation to the group without hypouricemia, no differences were observed between the various parameters studied including the z-DMO value, with the exception of fractional excretion and tubular urate reabsorption although plasmatic uric acid levels were still significantly lower. CONCLUSION: Our patients with hypercalciuria and hypouricemia would be affected by a variant of idiopathic hypercalciuria in which, due to an unknown cause, the proximal tubular reabsorption of urate is modestly reduced and improves over time. Hypouricemia with hypercalciuria and decreased bone density may not be a specific entity.

Alteration in maternal serum uric acid levels in pre-eclampsia and associated perinatal outcomes: a cross-sectional study in Ghana.

Introduction: pre-eclampsia (PE) is a multisystemic pregnancy-specific hypertensive disorder associated with significant adverse maternal and perinatal outcomes. Maternal serum uric acid level is hypothesized as a reliable marker for predicting the severity and adverse outcomes of pre-eclampsia and facilitating clinical decisions. This study explored the association between maternal serum uric acid and adverse pregnancy outcomes in pre-eclampsia. Methods: a cross-sectional study involving women diagnosed with pre-eclampsia was conducted at Korle-Bu Teaching Hospital (KBTH), a tertiary hospital in Ghana. Descriptive analyses were performed and multivariable logistic regression model was used to explore the association between maternal serum uric acid levels and pregnancy outcomes using R software. Results: we included 100 women with pre-eclampsia comprising 79% and 21% preterm and term pre-eclampsia respectively and with mean gestational age (GA) at diagnosis of 32.35±2.66 weeks and 35.96±1.94 weeks respectively. The mean maternal age of preterm and term pre-eclampsia groups was 29.81±5.29 years and 29.46±5.78 years respectively. Hyperuricemia (serum uric acid >375 µmol/L) occurred in 61% of the pre-eclamptic women. The mean gestational age (in weeks) at diagnosis was significantly lower in the pre-eclamptic women with hyperuricemia compared with those with normal levels of uric acid (33.51±3.03 versus 34.80±2.71). There was a significant negative association (moderate correlation) between maternal serum uric acid levels and birth weight (R= -0.34, p < 0.001) in pre-eclampsia; the statistical significance was limited to preterm only (Pearson R= -0.39, p-value <0.001) but not term pre-eclampsia. Hyperuricemia was significantly associated with low birth weight [aOR: 3.222 (95% CI: 1.098, 10.393)], caesarean section [aOR: 2.281 (95% CI: 1.084, 7.568)] and severe diastolic pressure at birth [aOR: 3.517 (95% CI: 1.123, 11.939)]. Conclusion: hyperuricemia in pre-eclampsia was significantly associated with both maternal (caesarean section and severe hypertension) and neonatal (low birth weight) adverse outcomes. Hyperuricemia seems clinically useful in predicting pregnancy outcomes, especially in preterm pre-eclampsia. Further longitudinal study is recommended in exploring the clinical significance of maternal uric acid levels and pregnancy outcomes in pre-eclampsia.

Effect and mechanism of Yiqing decoction on hyperuricemia rats.

This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.

Joint association of serum urate and healthy diet with chronic obstructive pulmonary disease incidence: results from the UK Biobank study.

Background: The role of serum urate (SU) levels in the development of chronic obstructive pulmonary disease (COPD) remains a topic of debate, and it is unclear whether a healthy diet can mitigate the impact of SU on COPD risk. The objective of this study is to examine whether and to what extent a healthy diet can reduce the risk of COPD in relation to SU levels. Methods: The cohort analysis included 155 403 participants from the UK Biobank. SU levels were measured at the time of recruitment. A healthy diet score was calculated based on the consumption of vegetables, fruits, fish, processed meats, unprocessed red meat, whole grains, and refined grains. The Cox proportional hazards model was used to analyze the associations between SU levels, a healthy diet score, and the risk of COPD. Results: During a follow-up period of 1 409 969 person-years, 2918 incident cases of COPD were identified. Compared with the lowest SU level group, the hazard ratio (HR) and 95% confidence interval (CI) for COPD were 1.17 (1.03, 1.34) for participants with the highest SU level (hyperuricemia), indicating a positive association. Additionally, a dose-response relationship was observed between SU levels and the incidence of COPD (P-value for overall <0.0001). In the combined effect analysis, compared to individuals with high SU (hyperuricemia) + a low diet score (diet score <4), those with normal SU + a high diet score (diet score ≥4) had a HR (95% CI) of 0.75 (0.65, 0.87) for COPD. Conclusions: In summary, there is a positive association between SU levels and the risk of COPD. Furthermore, a healthier diet can mitigate the risk of COPD associated with high SU levels.

Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

Colorimetric and fluorometric determination of uric acid by a suspension-based assay using enzyme-immobilized micro-sized particles.

Daily monitoring of serum uric acid levels is very important to provide appropriate treatment according to the constitution and lifestyle of individual hyperuricemic patients. We have developed a suspension-based assay to measure uric acid by adding a sample solution to the suspension containing micro-sized particles immobilized on uricase and horseradish peroxidase (HRP). In the proposed method, the mediator reaction of uricase, HRP, and uric acid produces resorufin from Amplex red. This resorufin is adsorbed onto enzyme-immobilized micro-sized particles simultaneously with its production, resulting in the red color of the micro-sized particles. The concentration of resorufin on the small surface area of the microscopic particles achieves a colorimetric analysis of uric acid with superior visibility. In addition, ethanol-induced desorption of resorufin allowed quantitative measurement of uric acid using a 96-well fluorescent microplate reader. The limit of detection (3σ) and RSD (n = 3) were estimated to be 2.2 × 10-2 µg/mL and ≤ 12.1%, respectively. This approach could also be applied to a portable fluorometer.

Elevated Serum Xanthine Oxidase and Its Correlation with Antioxidant Status in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged. Several studies reported that oxidative stress is a key modulator in the development of PD. This condition occurs due to excess reactive oxygen species (ROS) production in the cellular system and the incapability of antioxidants to neutralize it. In this study, we focused on the pathology of PD by measuring serum xanthine oxidase (XO) activity, which is an enzyme that generates ROS. Interestingly, the serum XO activity of patients with PD was markedly upregulated compared to patients with other neurological diseases (ONDs) as a control. Moreover, serum XO activity in patients with PD showed a significant correlation with the disease severity based on the Hoehn and Yahr (HY) stages. The investigation of antioxidant status also revealed that serum uric acid levels were significantly lower in the severe group (HY ≥ 3) than in the ONDs group. Together, these results suggest that XO activity may contribute to the development of PD and might potentially be a biomarker for determining disease severity in patients with PD.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.